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给老鼠喂食芸薹属蔬菜会导致许多组织中形成特征性的 DNA 加合物(来自 1-甲氧基-3-吲哚甲基葡萄糖硫苷)。

Feeding Brassica vegetables to rats leads to the formation of characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate) in many tissues.

机构信息

German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, 14558, Nuthetal, Germany.

Department Food Safety, Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.

出版信息

Arch Toxicol. 2022 Mar;96(3):933-944. doi: 10.1007/s00204-021-03216-8. Epub 2022 Jan 7.

DOI:10.1007/s00204-021-03216-8
PMID:34997255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8850215/
Abstract

Juices of Brassica vegetables are mutagenic and form characteristic DNA adducts in bacteria and mammalian cells. In this study, we examined whether such adducts are also formed in vivo in animal models. Rats fed raw broccoli ad libitum in addition to normal laboratory chow for 5 weeks showed one major adduct spot and sometimes an additional minor adduct spot in liver, kidney, lung, blood and the gastrointestinal tract, as determined by P-postlabelling/thin-layer chromatography. Adducts with the same chromatographic properties were formed when herring sperm DNA (or dG-3'-phosphate) was incubated with 1-methoxy-3-indolylmethyl glucosinolate (phytochemical present in Brassica plants), in the presence of myrosinase (plant enzyme that hydrolyses glucosinolates to bioactive breakdown products). UPLC-MS/MS analysis corroborated this finding: 1-Methoxy-3-indolylmethyl-substituted purine nucleosides were detected in the hepatic DNA of broccoli-fed animals, but not in control animals. Feeding raw cauliflower led to the formation of the same adducts. When steamed rather than raw broccoli was used, the adduct levels were essentially unchanged in liver and jejunum, but elevated in large intestine. Due to inactivation of myrosinase by the steaming, higher levels of the glucosinolates may have reached the large bowl to be activated by glucosidases from intestinal bacteria. In conclusion, the consumption of common Brassica vegetables can lead to the formation of substantial levels of DNA adducts in animal models. The adducts can be attributed to a specific phytochemical, neoglucobrassicin (1-methoxy-3-indolylmethyl glucosinolate).

摘要

甘蓝类蔬菜的汁液具有诱变作用,并在细菌和哺乳动物细胞中形成特征性的 DNA 加合物。在这项研究中,我们研究了这种加合物是否也在动物模型中体内形成。大鼠在正常实验室饲料之外自由摄入生西兰花 5 周,结果显示肝脏、肾脏、肺、血液和胃肠道中存在一个主要的加合物斑点,有时还存在一个额外的次要加合物斑点,这是通过 P-后标记/薄层层析法确定的。当鲱鱼精子 DNA(或 dG-3'-磷酸)与 1-甲氧基-3-吲哚甲基葡萄糖硫苷(存在于甘蓝植物中的植物化学物质)在植物酶(水解葡萄糖硫苷产生生物活性分解产物的酶)存在下孵育时,会形成具有相同色谱性质的加合物。UPLC-MS/MS 分析证实了这一发现:在喂食西兰花的动物的肝 DNA 中检测到 1-甲氧基-3-吲哚甲基取代的嘌呤核苷,但在对照动物中未检测到。喂食生花椰菜也会形成相同的加合物。当使用蒸而不是生西兰花时,肝脏和空肠中的加合物水平基本不变,但大肠中的加合物水平升高。由于蒸制使辣根过氧化物酶失活,更多的葡萄糖硫苷可能到达大肠,被肠道细菌的糖苷酶激活。总之,食用常见的甘蓝类蔬菜会导致动物模型中形成大量的 DNA 加合物。加合物可以归因于一种特定的植物化学物质,新葡萄糖异硫氰酸盐(1-甲氧基-3-吲哚甲基葡萄糖硫苷)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/7c22c8eb22db/204_2021_3216_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/afa1086284e3/204_2021_3216_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/9e9ec085e84f/204_2021_3216_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/04fa4fa74580/204_2021_3216_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/3320f3a8b3df/204_2021_3216_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/7c22c8eb22db/204_2021_3216_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/afa1086284e3/204_2021_3216_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/9e9ec085e84f/204_2021_3216_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/04fa4fa74580/204_2021_3216_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/3320f3a8b3df/204_2021_3216_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac7/8850215/7c22c8eb22db/204_2021_3216_Fig4_HTML.jpg

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2
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Nature. 2019 Feb;566(7743):249-253. doi: 10.1038/s41586-019-0899-7. Epub 2019 Jan 30.
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Data-Independent Mass Spectrometry Approach for Screening and Identification of DNA Adducts.
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Anal Chem. 2017 Nov 7;89(21):11728-11736. doi: 10.1021/acs.analchem.7b03208. Epub 2017 Oct 18.
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Glucosinolates Are Mainly Absorbed Intact in Germfree and Human Microbiota-Associated Mice.硫代葡萄糖苷主要以完整形式在无菌和人共生微生物相关小鼠中被吸收。
J Agric Food Chem. 2015 Sep 30;63(38):8418-28. doi: 10.1021/acs.jafc.5b02948. Epub 2015 Sep 22.
5
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Food Chem Toxicol. 2014 May;67:10-6. doi: 10.1016/j.fct.2014.02.008. Epub 2014 Feb 14.
8
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Chem Res Toxicol. 2014 Feb 17;27(2):188-99. doi: 10.1021/tx400277w. Epub 2014 Jan 14.
9
A secondary metabolite of Brassicales, 1-methoxy-3-indolylmethyl glucosinolate, as well as its degradation product, 1-methoxy-3-indolylmethyl alcohol, forms DNA adducts in the mouse, but in varying tissues and cells.十字花目植物的一种次生代谢产物,1-甲氧基-3-吲哚甲基硫代葡萄糖苷及其降解产物1-甲氧基-3-吲哚甲醇,在小鼠体内会形成DNA加合物,但在不同组织和细胞中的情况有所不同。
Arch Toxicol. 2014 Mar;88(3):823-36. doi: 10.1007/s00204-013-1149-7. Epub 2013 Oct 24.
10
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